Controlled release of active pharmaceutical ingredients, also named biologically active agents or therapeutically active agents, has become essential in treatments of humans and animals. Especially of interest is controlled release of active pharmaceutical ingredients locally in a body, such as in tissues or organs for either direct on-site treatment or for systemic uptake.
In recent years, a number of bioresorbable polymers fabricated into product shapes as microspheres, strands, rods and the like have been developed for this reason. The active pharmaceutical ingredient is incorporated into the interior of the polymer product and is after administration to the human or animal body slowly released by different mechanisms. One of the downsides of these products is the laborious process of incorporating the active ingredient in their interior, which may involve either organic solvents or elevated temperatures. These processes can result in the inactivation of the active ingredient during the process.
Numerous examples of liquid BAB block copolymers can be found in literature. Disadvantages of the prior art block copolymers are, however, that they are used in combination with solvent or liquid polymer additives to make injectable pharmaceutical compositions. In some cases the BAB block copolymers have rather high molecular weights and low molecular weight polymers like for example polyethylene glycol are added to make the composition injectable. In other cases the liquid BAB block copolymer are used as plasticizers for higher molecular weight block copolymers to make an injectable composition and/or to dissolve an API in the liquid polymer. Addition of these low molecular weight polymers give rise to high burst releases, and an unwanted fast release of the low molecular weight polymer, which may give negative physiological side effects. The incorporation of hydrophilic API's in these systems is also troublesome. In some examples water is added and mixed through the liquid polymer, which however show burst release and relatively short release times of the hydrophilic API. In yet many other cases water is added to prepare thermoreversible gels, which however show burst release and relative short release times of the hydrophilic API.